The importance of metabolic changes associated with contraction in the activation of glycogen synthase (GS) during recovery from exercise in human skeletal muscle has been investigated. Subjects underwent two experimental treatments: 15 s of ischaemic isometric contraction at 66% of maximal force, and 40 min circulatory occlusion. Biopsies were taken from the quadriceps femoris muscle at rest, at the end of each treatment, and 5 min post-treatment. The decreases in phosphocreatine (approximately 50%), and increases in glucose 6-phosphate (approximately 3-fold) and lactate (approximately 8-fold) were similar during contraction and occlusion, indicating similar degrees of anaerobic ATP turnover and glycogen breakdown. Glycogen breakdown during each treatment was estimated to correspond to < 5% of the basal muscle glycogen content. GS fractional activity decreased approximately 10% after contraction and approximately 30% after occlusion (P < 0.05 vs. contraction). During recovery from contraction, GS fractional activity increased to 20% above the rest value, whereas no further change occurred during recovery from occlusion (P < 0.001 vs. recovery from contraction). These data demonstrate that the increase in GS fractional activity during recovery from isometric contraction does not require significant glycogen breakdown during the contraction, and is not a consequence of the measured metabolic changes associated with the contraction.